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Limb girdle myopathies (LGM) form a group of clinically and genetically heterogeneous diseases responsible of progressive weakness predominantly affecting the shoulder and pelvic girdles muscles. Duchenne muscular dystrophy (DMD) and sarcoglycanopathies have been for decades recognized as the main myopathy's subtypes in Tunisia. We have performed a retrospective study including the patients diagnosed with LGM since January 2014 until December 2023, with an age onset of at least 2 years old. We have reviewed the full family history and medical data. All of the patients underwent CK levels dosage, EMG, muscle biopsy and molecular genetic studies. We excluded the patients diagnosed with DMD. We obtained a cohort of 44 patients, 60% of cases were males and 40% were females. Targeted genetic diagnosis of sarcoglycanopathies was performed in 50% of our patients. LGMDR5 was the most frequent subtype, with three identified variants of mutations in the SGCG gene: c521 del T (hot-spot mutation), c582 ins A and c525 del T. In the other half of our cohort, larger genetic analysis, with a LGMD panel or a whole exome sequencing (WES), showed mutations in the CAPN3 (LGMDR1), DYSF (LGMDR2), FKRP (LGMDR9), POMT1 (LGMDR11), GMPPB (LGMDR19), and COL6A1 (LGMDR22) genes. In addition, mutations in new genes that were not previously described in Tunisia were also identified: TITIN, RYR1, LMNA, GGPS1, PYROXD1, COL13A1 and VMA21. We emphasize the genetic variability of LGM in Tunisia and North Africa. The list of the implicated genes is continuously extending, exceeding so far the sarcoglycanopathies group. [ABSTRACT FROM AUTHOR]

Rigid spine syndrome is a classically childhood-onset progressive and non-painful limitation of the neck and trunk flexion leading to postural abnormalities. Myopathies related to mutations in EMD, LMNA, SEPN1, COL6 and FHL1 genes are the most frequent causes. We report the case of a 10-year-old boy, born of consanguineous Libyan parents, who presents since the age of 7 years difficulties in the neck extension and progressive spine straightness. Motor and intellectual development were normal. On examination he showed a cachectic phenotype, spontaneous trunk flexion, prominent rigid spine, scapular winging, and flat retracted thorax. We found no spontaneous limb joint contractures. Weakness was more prominent in the cervicodorsal spine, and mild in the proximal upper limb muscles. Amyotrophy involved preferentially neck, trunk, and deltoid muscles. The patient is ambulant; however, his sport performance was limited and often complains about excessive fatigue. Creatine kinase levels were normal, and EMG showed myogenic pattern. On the deltoid muscle biopsy, we found the presence of numerous nemaline bodies confirming the diagnosis of nemaline myopathy (NM). The whole exome sequencing revealed the presence of a homozygous variant in the Cofilin-2 (CFL2) gene, a rare cause of autosomal recessive NM. The variant we found: NM_021914.7:c.115T>G p.(Cys39Gly), is classified as a variant of uncertain significance (class 3) according to the recommendations of ACMG. However, we considered it as a potentially relevant result, since the CFL2 gene is reported essentially in patients with NM, and the presence of multiple nemaline bodies on the patient's muscle biopsy. [ABSTRACT FROM AUTHOR]

Musculoskeletal hydatid disease is rare and can be located anywhere but most commonly the bone and muscles of the spine, pelvis, then the lower limbs. Imaging is essential for its diagnosis, performing the pre-therapeutic assessment, guiding possible percutaneous treatments, and providing post-therapeutic follow-up. Musculoskeletal hydatidosis can take several forms that may suggest other infections and tumors or pseudotumors. MRI and CT are superior for its diagnosis but ultrasound and radiography remain the most accessible examinations in developing countries where this parasitosis is endemic. In this review, we provide an overview of this disease and describe its different imaging patterns in soft tissue and bone involvement that should be sought to support the diagnosis., (© 2024. The Author(s), under exclusive licence to International Skeletal Society (ISS).)

Introduction: Immune checkpoint blockers have revolutionized the first-line treatment of advanced non-small-cell lung cancer (NSCLC). Pembrolizumab, an anti-PD-1 monoclonal antibody, is a standard therapy either alone or in combination with chemotherapy (chemo-IO). The current study explores the efficacy and safety of pembrolizumab with carboplatin and weekly paclitaxel in a cohort of frail patients., Methods: A monocentric retrospective study was conducted between 22 September 2020 and 19 January 2023 regarding patients with stage IV NSCLC treated with chemo-IO combination: carboplatin (AUC 5 mg/mL/min; Q4W), weekly paclitaxel (90 mg/m 2 on days 1, 8, and 15), and pembrolizumab (200 mg Q4W). The primary objective was real-world progression-free survival (rwPFS). Secondary objectives were overall survival (OS), toxicity profile, and outcomes based on histological subtype., Results: A total of 34 patients (20 squamous and 14 non-squamous NSCLC) benefited from the chemo-IO regimen for frail patients; 41.9% had an ECOG-PS = 2. The median age was 75.5 years. We observed an overall response rate (ORR) of 55.9%. Notably, squamous NSCLC exhibited a significantly higher ORR (80%) than non-squamous NSCLC (21.4%); p = 0.001. The median rw-PFS was 10.6 months (95% CI [6.0, NA]), with 6- and 12-month rw-PFS rates of 69% and 45.8%, respectively. The median OS was not reached, with 12- and 18-month OS rates of 75.6% and 61.4%, respectively. The median number of maintenance cycles of pembrolizumab was 5 (0; 27). Nine patients (26.5%) experienced a toxicity related to chemotherapy leading to a reduction of the dose administered and, in five patients (14.7%), to the permanent discontinuation of chemotherapy. Six patients (17.6%) had an immune-related adverse event leading to the discontinuation of immunotherapy., Discussion: Pembrolizumab plus carboplatin and weekly paclitaxel demonstrates promising efficacy and safety in frail patients with metastatic NSCLC, especially for ORR in sq-NSCLC. Prospective studies focusing on frail populations are warranted in order to validate these findings and optimize therapeutic strategies in the first-line setting.

Lung cancer is the leading cause of cancer mortality in the world. It greatly affects the patients' quality of life, and is thus a challenge for the daily practice in respiratory medicine. Advances in the genetic knowledge of thoracic tumours' mutational landscape, and the development of targeted therapies and immune checkpoint inhibitors, have led to a paradigm shift in the treatment of lung cancer and pleural mesothelioma. During the 2023 European Respiratory Society Congress in Milan, Italy, experts from all over the world presented their high-quality research and reviewed best clinical practices. Lung cancer screening, management of early stages of lung cancer, application of artificial intelligence and biomarkers were discussed and they will be summarised here., Competing Interests: Conflict of interest: The authors have nothing to disclose., (Copyright ©The authors 2024.)